• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

AMPK 激活通过重编葡萄糖和脂质代谢诱导 RALDH+ 耐受性树突状细胞。

AMPK activation induces RALDH+ tolerogenic dendritic cells by rewiring glucose and lipid metabolism.

机构信息

Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands.

Department Biomolecular Health Sciences, Utrecht University, Utrecht, Netherlands.

出版信息

J Cell Biol. 2024 Oct 7;223(10). doi: 10.1083/jcb.202401024. Epub 2024 Aug 8.

DOI:10.1083/jcb.202401024
PMID:39115541
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11310580/
Abstract

Dendritic cell (DC) activation and function are underpinned by profound changes in cellular metabolism. Several studies indicate that the ability of DCs to promote tolerance is dependent on catabolic metabolism. Yet the contribution of AMP-activated kinase (AMPK), a central energy sensor promoting catabolism, to DC tolerogenicity remains unknown. Here, we show that AMPK activation renders human monocyte-derived DCs tolerogenic as evidenced by an enhanced ability to drive differentiation of regulatory T cells, a process dependent on increased RALDH activity. This is accompanied by several metabolic changes, including increased breakdown of glycerophospholipids, enhanced mitochondrial fission-dependent fatty acid oxidation, and upregulated glucose catabolism. This metabolic rewiring is functionally important as we found interference with these metabolic processes to reduce to various degrees AMPK-induced RALDH activity as well as the tolerogenic capacity of moDCs. Altogether, our findings reveal a key role for AMPK signaling in shaping DC tolerogenicity and suggest AMPK as a target to direct DC-driven tolerogenic responses in therapeutic settings.

摘要

树突状细胞 (DC) 的激活和功能是由细胞代谢的深刻变化所支撑的。有几项研究表明，DC 促进耐受的能力依赖于分解代谢。然而，AMP 激活的蛋白激酶 (AMPK)——促进分解代谢的中央能量传感器——对 DC 耐受能力的贡献尚不清楚。在这里，我们表明 AMPK 的激活使人类单核细胞衍生的 DC 具有耐受性，这表现在增强了诱导调节性 T 细胞分化的能力，这一过程依赖于 RALDH 活性的增加。这伴随着几种代谢变化，包括甘油磷脂的分解增加、线粒体分裂依赖性脂肪酸氧化增强以及葡萄糖分解代谢上调。这种代谢重编程在功能上是重要的，因为我们发现干扰这些代谢过程会降低 AMPK 诱导的 RALDH 活性以及 moDC 的耐受性。总的来说，我们的发现揭示了 AMPK 信号在塑造 DC 耐受性中的关键作用，并表明 AMPK 可作为在治疗环境中指导 DC 驱动的耐受反应的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/edadd09c5a93/JCB_202401024_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/bb26832eeefe/JCB_202401024_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/5610206d8fca/JCB_202401024_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/3f64f7152972/JCB_202401024_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/e0624070a101/JCB_202401024_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/d2f8ab4d2fff/JCB_202401024_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/ed2ac311c083/JCB_202401024_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/c990b752e655/JCB_202401024_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/4de780a407fc/JCB_202401024_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/4769b47e907e/JCB_202401024_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/071a69cbdc1c/JCB_202401024_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/edadd09c5a93/JCB_202401024_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/bb26832eeefe/JCB_202401024_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/5610206d8fca/JCB_202401024_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/3f64f7152972/JCB_202401024_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/e0624070a101/JCB_202401024_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/d2f8ab4d2fff/JCB_202401024_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/ed2ac311c083/JCB_202401024_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/c990b752e655/JCB_202401024_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/4de780a407fc/JCB_202401024_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/4769b47e907e/JCB_202401024_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/071a69cbdc1c/JCB_202401024_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/767f/11310580/edadd09c5a93/JCB_202401024_Fig5.jpg

相似文献

1
AMPK activation induces RALDH+ tolerogenic dendritic cells by rewiring glucose and lipid metabolism.AMPK 激活通过重编葡萄糖和脂质代谢诱导 RALDH+ 耐受性树突状细胞。
J Cell Biol. 2024 Oct 7;223(10). doi: 10.1083/jcb.202401024. Epub 2024 Aug 8.
2
High mitochondrial respiration and glycolytic capacity represent a metabolic phenotype of human tolerogenic dendritic cells.高线粒体呼吸和糖酵解能力代表了人类耐受性树突状细胞的一种代谢表型。
J Immunol. 2015 Jun 1;194(11):5174-86. doi: 10.4049/jimmunol.1303316. Epub 2015 Apr 27.
3
The Long Noncoding RNA MALAT1 Induces Tolerogenic Dendritic Cells and Regulatory T Cells miR155/Dendritic Cell-Specific Intercellular Adhesion Molecule-3 Grabbing Nonintegrin/IL10 Axis.长链非编码 RNA MALAT1 通过 miR155/树突状细胞特异性细胞间黏附分子 3 抓取非整合素/IL10 轴诱导耐受树突状细胞和调节性 T 细胞。
Front Immunol. 2018 Aug 13;9:1847. doi: 10.3389/fimmu.2018.01847. eCollection 2018.
4
Adipose-derived stem cell modulate tolerogenic dendritic cell-induced T cell regulation is correlated with activation of Notch-NFκB signaling.脂肪来源的干细胞调节耐受诱导树突状细胞诱导的 T 细胞调节与 Notch-NFκB 信号的激活相关。
Cytotherapy. 2024 Aug;26(8):890-898. doi: 10.1016/j.jcyt.2024.03.482. Epub 2024 Mar 29.
5
Regulation of Tolerogenic Features on Dexamethasone-Modulated MPLA-Activated Dendritic Cells by MYC.MYC 调控地塞米松调节的 MPLA 激活的树突状细胞的耐受特征。
Front Immunol. 2019 May 28;10:1171. doi: 10.3389/fimmu.2019.01171. eCollection 2019.
6
NCoR1 controls immune tolerance in conventional dendritic cells by fine-tuning glycolysis and fatty acid oxidation.NCoR1 通过精细调节糖酵解和脂肪酸氧化来控制常规树突状细胞中的免疫耐受。
Redox Biol. 2023 Feb;59:102575. doi: 10.1016/j.redox.2022.102575. Epub 2022 Dec 16.
7
Plant-Derived Polyphenols Modulate Human Dendritic Cell Metabolism and Immune Function via AMPK-Dependent Induction of Heme Oxygenase-1.植物源多酚通过 AMPK 依赖性诱导血红素加氧酶-1 来调节人树突状细胞代谢和免疫功能。
Front Immunol. 2019 Mar 1;10:345. doi: 10.3389/fimmu.2019.00345. eCollection 2019.
8
Allergoid-mannan conjugates reprogram monocytes into tolerogenic dendritic cells via epigenetic and metabolic rewiring.变应原甘露聚糖缀合物通过表观遗传和代谢重编程将单核细胞转化为耐受性树突状细胞。
J Allergy Clin Immunol. 2022 Jan;149(1):212-222.e9. doi: 10.1016/j.jaci.2021.06.012. Epub 2021 Jun 18.
9
Cisplatin induces tolerogenic dendritic cells in response to TLR agonists via the abundant production of IL-10, thereby promoting Th2- and Tr1-biased T-cell immunity.顺铂通过大量产生白细胞介素-10对Toll样受体激动剂作出反应，诱导产生耐受性树突状细胞，从而促进偏向于辅助性T细胞2型和1型调节性T细胞的免疫反应。
Oncotarget. 2016 Jun 7;7(23):33765-82. doi: 10.18632/oncotarget.9260.
10
Tolerogenic signaling by pulmonary CD1c+ dendritic cells induces regulatory T cells in patients with chronic obstructive pulmonary disease by IL-27/IL-10/inducible costimulator ligand.肺脏 CD1c+树突状细胞的耐受信号通过 IL-27/IL-10/诱导共刺激配体诱导慢性阻塞性肺疾病患者中的调节性 T 细胞。
J Allergy Clin Immunol. 2014 Oct;134(4):944-954.e8. doi: 10.1016/j.jaci.2014.05.045. Epub 2014 Jul 19.

本文引用的文献

1
LAG-3, TIM-3, and TIGIT: Distinct functions in immune regulation.LAG-3、TIM-3 和 TIGIT：免疫调节中的不同功能。
Immunity. 2024 Feb 13;57(2):206-222. doi: 10.1016/j.immuni.2024.01.010.
2
Pyruvate metabolism controls chromatin remodeling during CD4 T cell activation.丙酮酸代谢在 CD4 T 细胞激活过程中控制染色质重塑。
Cell Rep. 2023 Jun 27;42(6):112583. doi: 10.1016/j.celrep.2023.112583. Epub 2023 Jun 1.
3
Long-term tolerance to skin commensals is established neonatally through a specialized dendritic cell subgroup.新生儿期通过一种特殊的树突状细胞亚群建立对皮肤共生菌的长期耐受。
Immunity. 2023 Jun 13;56(6):1239-1254.e7. doi: 10.1016/j.immuni.2023.03.008. Epub 2023 Apr 6.
4
Characterization of Dendritic Cell Metabolism by Flow Cytometry.流式细胞术分析树突状细胞代谢特性。
Methods Mol Biol. 2023;2618:219-237. doi: 10.1007/978-1-0716-2938-3_16.
5
Metabolic programming and immune suppression in the tumor microenvironment.代谢编程与肿瘤微环境中的免疫抑制
Cancer Cell. 2023 Mar 13;41(3):421-433. doi: 10.1016/j.ccell.2023.01.009. Epub 2023 Feb 16.
6
The role of tolerogenic dendritic cells in systematic lupus erythematosus progression and remission.耐受性树突状细胞在系统性红斑狼疮进展和缓解中的作用。
Int Immunopharmacol. 2023 Feb;115:109601. doi: 10.1016/j.intimp.2022.109601. Epub 2022 Dec 24.
7
NCoR1 controls immune tolerance in conventional dendritic cells by fine-tuning glycolysis and fatty acid oxidation.NCoR1 通过精细调节糖酵解和脂肪酸氧化来控制常规树突状细胞中的免疫耐受。
Redox Biol. 2023 Feb;59:102575. doi: 10.1016/j.redox.2022.102575. Epub 2022 Dec 16.
8
New insights into activation and function of the AMPK.对AMPK激活及功能的新见解。
Nat Rev Mol Cell Biol. 2023 Apr;24(4):255-272. doi: 10.1038/s41580-022-00547-x. Epub 2022 Oct 31.
9
Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells.不同的代谢状态指导炎症性和耐受性树突状细胞的成熟。
Nat Commun. 2022 Sep 2;13(1):5184. doi: 10.1038/s41467-022-32849-1.
10
Phosphatidylcholine-Derived Lipid Mediators: The Crosstalk Between Cancer Cells and Immune Cells.磷脂酰胆碱衍生的脂质介质：癌细胞与免疫细胞的串扰。
Front Immunol. 2022 Feb 15;13:768606. doi: 10.3389/fimmu.2022.768606. eCollection 2022.